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Biomedical subjects

B Chin

Publications and source records attributed to B Chin.

At least 19 recordsLinked to original sources
PubMed2001

Efficacy and safety of combination simvastatin and colesevelam in patients with primary hypercholesterolemia.

PURPOSE: To examine the efficacy and safety of colesevelam hydrochloride, a novel, nonsystemic, lipid-lowering agent, when coadministered with starting doses of simvastatin in a multicenter, randomized, double-blind, placebo-controlled trial. PATIENTS AND METHODS: Subjects with hypercholesterolemia (plasma low density lipoprotein [LDL] cholesterol level > 160 mg/dL and triglyceride level < or = 300 mg/dL) were randomly assigned to receive daily doses of placebo (n = 33), colesevelam 3.8 g (recommended dose, n = 37), simvastatin 10 mg (n = 35), colesevelam 3.8 g with simvastatin 10 mg (n = 34), colesevelam 2.3 g (low dose, n = 36), simvastatin 20 mg (n = 39), or colesevelam 2.3 g with simvastatin 20 mg (n = 37), for 6 weeks. RESULTS: Mean LDL cholesterol levels decreased relative to baseline in the placebo group (P < 0.05) and in all active treatment groups (P < 0.0001). For groups treated with combination therapy, the mean reduction in LDL cholesterol level was 42% (-80 mg/dL; P < 0.0001 compared with baseline), which exceeded the reductions for simvastatin 10 mg (-26%, -48 mg/dL) or 20 mg (-34%, -61 mg/dL) alone, or for colesevelam 2.3 g (-8%, -17 mg/dL) or 3.8 g (-16%, -31 mg/dL) alone (P < 0.001). The effects of combination therapy on serum HDL cholesterol and triglyceride levels were similar to those for simvastatin alone. Side effects were similar among treatment groups, and there were no clinically important changes in laboratory parameters. CONCLUSION: Coadministration of colesevelam and simvastatin was effective and well tolerated, providing additive reductions in LDL cholesterol levels compared with either agent alone.

Adult↗
PubMed2001

Comparison of myocardial oxygen consumption using 11C acetate positron emission tomography scanning in a working and non-working heart transplant model.

OBJECTIVE: In acute cardiac rejection, changes in myocardial oxygen consumption occur; non-invasive detection of these metabolic changes would have obvious clinical utility. In the classic cervical, heterotopic, canine, transplant model, the heart is non-working. It has a low myocardial oxygen consumption. Creation of a working model with normal myocardial oxygen consumption would enhance validity of non-human studies. METHODS: Clearance of 11C acetate was determined by positron emission tomography (PET) scanning and compared with myocardial oxygen consumption in normal and transplanted canine hearts. Donor hearts from mongrel dogs (2.5-3 kg; n=4) were transplanted into the neck of adult beagles (12-15 kg; n=4), no immunosuppression was given. Two non-working hearts were modified to eject only coronary flow via the right ventricle. In two hearts, a novel working model was created with aortic regurgitation to load the left ventricle. Working and non-working hearts underwent PET scanning on post-operative days 2 and 4. Normal dog hearts (n=2) and native hearts of transplanted dogs (n=3) were used to validate the scanning technique. Coronary sinus and aortic oxygen saturation data along with myocardial blood flow (radiolabeled microspheres) confirmed that clearance of 11C acetate in normal and transplanted hearts followed a bi-exponential model. RESULTS: Myocardial oxygen consumption was correlated with the rate constant of 11C acetate rapid phase clearance (r=0.91) in normal and transplanted hearts. The working hearts had increased myocardial oxygen consumption compared to non-working hearts. CONCLUSIONS: This study (1) introduces a model of a working heterotopic cardiac transplantation with near-normal oxygen consumption; and (2) demonstrates that regional myocardial oxygen consumption in transplanted hearts can be detected by 11C acetate PET.

Acetates↗
PubMed2001

Four-dimensional dielectric property image obtained from electron spectroscopic imaging series.

We have demonstrated a new quantitative method to characterize two-dimensional distributions of energy-dependent dielectric function of materials from low loss electron spectroscopic image (ESI) series. Two problems associated with extracted image-spectrum from the low-loss image series, under-sampling and loss of energy resolution, were overcome by using fast Fourier transformation (FFT) interpolation and maximum entropy deconvolution method. In this study, Black Diamond/Si3N4/SiO2/Si-substrate dielectric layer designed for copper metallization was used as the sample. We show that the reconstructed (FFT interpolated and maximum entropy deconvoluted) image-spectrum obtained from ESI series images can be quantified with the same accuracy as conventional electron energy-loss spectroscopy spectra. Since the analysis of the dielectric function is sensitive to the local thickness of the specimen using Kramers-Kronig analysis, we also developed a new method to quantitatively determine the dielectric constant for low-k materials. We have determined the thickness of the Black Diamond using the extrapolated thickness method from the materials of known dielectric constants. Using Kramers-Kronig formula, the dielectric function map can be deduced from two-dimensional reconstructed single scattering spectra with providing the information of thickness. We proposed a four-dimensional data presentation for revealing the uniformity of the energy dependent property. The accuracy of our methods depends on the thickness determination and on the quality of the reconstructed spectra from the image series.

Journal Article↗
PubMed2001

Unstable angina following acute MI in a patient with bilateral coronary artery fistulae: an unusual presentation of coronary steal?

We report a 57-year-old woman with acute myocardial infarction and cardiac arrest who subsequently developed unstable angina. The possibility of a coronary steal syndrome contributing to her unstable angina arises in view of the presence of bilateral coronary artery fistulae between two atherosclerotic coronary arteries and the main pulmonary artery.

Acute Disease↗
PubMed2000

Targeted inhibition of wound-induced PAI-1 expression alters migration and differentiation in human epidermal keratinocytes.

In the adult epidermis, keratinocytes do not normally express the type-1 inhibitor of plasminogen activator (PAI-1). Basal epithelial cell-specific PAI-1 synthesis, however, accompanies epidermal wound repair in vivo in which PAI-1 transcripts and immunoreactive protein are confined to epithelial cells in the migrating tongue and the hyperproliferative zone. A model system using human keratinocytes (HaCaT cells) was developed to assess functional relationships between epithelial growth state transitions and PAI-1 expression. PAI-1 synthesis was maximal in low population density, exponentially growing HaCaT cultures; relative PAI-1 mRNA and protein levels progressively declined as cells attained, and were maintained in, a postconfluent condition. While the fraction of PAI-1(+) keratinocytes remained stable (at approximately 85-90% of the population) throughout the culture period, both PAI-1 mRNA abundance and mean cell-associated PAI-1 protein declined by >90% during prolonged (i.e., 8-day) growth arrest. Similar to epidermal trauma in vivo, scrape wounding of HaCaT monolayers resulted in the rapid and location-specific induction of PAI-1 protein (an increase of 11- to 16-fold relative to unwounded cultures) in cells immediately bordering the injury site. PAI-1 expression was evident in keratinocytes that comprised the opposed migrating fronts and remained elevated until wound closure. Down-regulation of PAI-1 synthesis in HaCaT cells transfected with an inducible LacSwitch-based antisense vector system markedly impaired both the rate and the extent of wound closure. All injuries created in antisense PAI-1 monolayers remained unhealed at day 8 postinjury compared to the 3-day complete repair typical of control cultures. Vector-driven modulation of PAI-1 synthesis was also associated with an increase in the percentage of suprabasal-type keratinocytes within the wound field. PAI-1 expression by migrating HaCaT cells appears necessary to maintain the basal epidermal phenotype and/or appropriate cell-to-substrate adhesion during injury repair.

Cell Differentiation↗
PubMed2000

Cariporide Aventis.

Cariporide is a sodium/hydrogen ion exchange inhibitor under development by Aventis Pharma, formerly Hoechst Marion Roussel (HMR), as a potential treatment for myocardial infarction (MI), ischemic damage due to angioplasty and reperfusion following thrombolysis. It is in phase II/III trials [221118]. Cariporide inhibits the interchange of sodium ions and protons in myocardial cells during unstable angina or MI when cells metabolize anerobically. This prevents lactic acid production and an increase in calcium levels which causes cardiac arrhythmias and heart tissue death [253616]. Approval filings in the US and EU had been scheduled for the second half of 1999 [309323]. In 1998, HMR expected that the drug would be launched in 2000, and would have a potential market in excess of DM 750 million [288651]. By May 2000, however, the launch date had been revised for between 2003 and 2004 [370971], [379336]. Aventis is expecting peak sales to be around $400 million [333420]. In March 1999, HMR reported that trials for MI had been suspended after results from the phase III GUARDIAN trial did not achieve statistical significance [353173]. In August 2000, however, a phase II trial in patients with acute MI was underway [379051]. A phase III trial in patients undergoing coronary artery bypass grafting (CABG) was expected to begin in early 2000 after the results of ongoing dose-optimization studies in CABG patients are known. As of May 2000, however, this trial had not begun, although based on promising CABG-related results of the GUARDIAN trial, the phase III trial in this indication is expected to begin in the first half of 2001 [370971]. There were also plans for the initiation of European phase II trials in acute MI patients; similar phase II trials are ongoing in Japan. In September 2000, Merrill Lynch predicated launch in 2003 [383742]. In February 1999, Lehman Brothers predicted a 70% probability that cariporide would reach market in the US/Europe and 50% probability that it would reach the Japanese market. They also predicted a US/European launch in 2000 with peak sales of $400 million in 2008 and a Japanese launch in 2002 with peak sales of $100 million [319225].

Anti-Arrhythmia Agents↗
PubMed1998

Solvent replacement for green processing.

The implementation of the Montreal Protocol, the Clean Air Act, and the Pollution Prevention Act of 1990 has resulted in increased awareness of organic solvent use in chemical processing. The advances made in the search to find "green" replacements for traditional solvents are reviewed, with reference to solvent alternatives for cleaning, coatings, and chemical reaction and separation processes. The development of solvent databases and computational methods that aid in the selection and/or design of feasible or optimal environmentally benign solvent alternatives for specific applications is also discussed.

Air Pollution↗
PubMed1997

Global cardiac function using fast breath-hold MRI: validation of new acquisition and analysis techniques.

Calculation of global cardiac function parameters has been validated using fast, segmented k-space, breath-hold, gradient-echo, magnetic resonance images. Images of phantoms, experimental animals, normal volunteers, and patients were acquired with a 1.5 T clinical scanner. Humans were imaged using two phased-array surface coils in multicoil mode. Myocardial contours were extracted using a new interactive, semi-automated method based on the active contour model method. Images were acquired in the short-axis orientation, and, using a new imaging and analysis strategy, in rotating plane long-axis orientations, to provide better definition of the valve planes and the apex, and also to reduce the number of slices (compared with the short-axis method) required to sample the whole heart. Validation was accomplished through calculation of the volumes of phantoms and left and right ventricular masses of animal hearts. Functional parameters from MRI were compared with those from echocardiograms and radionuclide angiograms in normal volunteers and patients, respectively.

Adult↗
PubMed1995

Proteinases of rat mast cells. Peritoneal but not intestinal mucosal mast cells express mast cell proteinase 5 and carboxypeptidase A.

Six basic proteins of 26 to 38 kDa with isoelectric points (pI) > or = 8.5 were abundant in proteins separated by two-dimensional SDS-PAGE from adult rat peritoneal mast cells (MC). One was identified previously as rat mast cell proteinase (RMCP) 1, a chymase of 26 to 28 kDa, pI > 9.0. Microsequence analyses showed that two polypeptides of about 29 and 30 kDa had NH2 terminal amino acid sequences homologous to mouse MC proteinase 5 (MCP-5), whereas the amino terminals of the 33, 35, and 36 kDa proteins were homologous to MC carboxypeptidase A (MC-CPA). Rabbit Abs produced against synthetic peptides of the identified NH2 terminal sequences were used in immunoblot studies. At least three proteins reacted with Abs to MC-CPA, whereas Abs to MCP-5 detected three adjacent polypeptides, rather than just the two identified by using microsequence analysis. Removal of oligosaccharide side chains using peptide:N-glycosidase F reduced the heterogeneity of each set of three polypeptides (MCP-5 and MC-CPA) to a band of each protein of a lower M(r). The serine proteinase inhibitor [3H]diisopropylfluorophosphate ([3H]DFP) bound to a proteinase of 30 to 35 kDa, which is probably MC tryptase (pI < or = 6.0). Immunoblot analysis of proteins from intestinal mucosal mast cells showed RMCP-2, but not RMCP-1, MCP-5, or MC-CPA. This is the first report of MCP-5 in the rat and of clearly distinguishable glycosylated forms of MC CPA. These proteinases appear to be restricted in their distribution to selected MC populations, but little is known about their functions.

Amidohydrolases↗
PubMed1995

MOMs (multiples of the median) and DADs (discriminant aneuploidy detection): improved specificity and cost-effectiveness of biochemical screening for aneuploidy with DADs.

OBJECTIVE: Our purpose was to assess the efficacy of double- and triple-screening paradigms for Down syndrome and to develop a more logical, statistical approach to risk prediction that will decrease the cost of screening and allow the incorporation of new parameters appropriately weighted for their contribution. STUDY DESIGN: Data from 24,504 patients who had biochemical screening for Down syndrome by single (alpha-fetoprotein), double (alpha-fetoprotein, beta-human chorionic gonadotropin), or triple screening (alpha-fetoprotein, beta-human chorionic gonadotropin, unconjugated estriol) who had complete outcome information were analyzed by (1) existing gaussian-based methods, (2) the Glasgow ratio method, and (3) a new statistical approach (i.e., directly adjusted data sets for discriminant aneuploidy detection [DADs]) RESULTS: By use of individual risk-based thresholds for "at risk" status, both double and triple screening performed far better than single screening, but the percentages of patients at risk varied widely. When the percentages at risk were held constant, the sensitivity of double and triple screenings was similar, suggesting that there are no benefits of using estriol as a third marker. For 25,000 patients the use of only alpha-fetoprotein and beta-human chorionic gonadotropin would save about $500,000, with no decrease in sensitivity. With the DADs approach a statistically sound model giving more stable estimates was developed that permits each factor to be analyzed for its own explained proportion of variance and allows each parameter to have different weighting. For this data set the same sensitivity was seen with, conservatively, a 1% reduction in the percentage of patients at risk, which would reduce by 250 the number of amniocenteses, at a further savings of about $400,000. CONCLUSIONS: By use of existing methods, double screening is equally as effective as triple screening, so that the expense of estriol is unnecessary. The DADs approach, by allowing for variable weighting of parameters, lowers the at risk percentage and will permit a much more flexible approach as new parameters become available. Changing to DADs and eliminating estriol should achieve higher specificity for the same sensitivity and save, conservatively, about $900,000 in this series. Extrapolated nationally, if confirmed, the annual savings could approach $72,000,000.

Adolescent↗
PubMed1995

Interferons differentially regulate histamine and TNF-alpha in rat intestinal mucosal mast cells.

Mast cell (MC) heterogeneity has been well characterized in the rat where it has been shown that connective tissue MC, often represented by peritoneal MC (PMC), and the intestinal mucosal MC (IMMC) exhibit many differences in mediator content and responsiveness to secretagogues and anti-allergic drugs. Pretreatment (20 hr) of PMC with interferon (IFN)-alpha/beta or IFN-gamma, significantly reduced antigen-stimulated histamine release. By contrast, for IMMC, the same IFN treatment did not modify antigen-stimulated histamine secretion. Although IFN treatment differentially modulates histamine secretion from PMC and IMMC, pretreatment of both MC types with IFN-alpha/beta or IFN-gamma inhibited their tumour-necrosis factor-alpha (TNF-alpha)-dependent cytotoxicity. In 20 hr of culture, IMMC spontaneously released 98 pg/10(6) MC of TNF-alpha, whereas PMC released about threefold more TNF-alpha, 282 pg/10(6) MC. In addition, direct assessment of stored TNF-alpha established that IMMC store less TNF-alpha (68 pg/10(6) MC) than PMC (404 pg/10(6) MC). In summary, TNF-alpha content of PMC and IMMC was different, but IFN inhibited TNF-alpha-dependent cytotoxicity by both MC types. By contrast, treatment with IFN-alpha/beta or IFN-gamma inhibits antigen-induced histamine secretion by PMC, but does not modify antigen-induced histamine secretion by IMMC. Thus, IFN differentially regulate the secretion of histamine and TNF-alpha in PMC and IMMC.

Animals↗
PubMed1993

Nutritional status of Kadazan children in a rural district in Sabah, Malaysia.

The nutritional status of 896 Kadazan children below 6 years of age from 23 villages of Tambunan District were studied. When stunting and wasting were defined as those who were below two standard deviations of height-for-age and weight-for-height (Waterlow et al, 1977) and based on the National Center for Health Statistics reference population, 67.6% of boys and 66.8% of girls were stunted while 12.3% of boys and 8.3% of girls were wasted. Weaning foods and toddler feeding practices were unsatisfactory. The role of health education on child care and feeding practices is emphasized.

Anthropometry↗
PubMed1988

Effects of isradipine, a new calcium antagonist, versus hydrochlorothiazide on serum lipids and apolipoproteins in patients with systemic hypertension.

The effect of isradipine versus hydrochlorothiazide on the lipid profile of 44 hypertensive patients was investigated in a double-blind, randomized, 2-center trial. Lipid profiles included total cholesterol, serum triglycerides, high density lipoprotein (HDL) cholesterol, HDL subclasses, (HDL2 and HDL3), low density lipoprotein cholesterol, very low density lipoprotein cholesterol, apolipoprotein A-1 and apolipoprotein B. Isradipine had no effect on the lipid profile in short- (4 and 10 week) or long-term (52 week) studies. Hydrochlorothiazide increased serum triglycerides in 11 of 13 patients by a mean of 8% for the group (p less than 0.05) in long-term (52 week) studies, and total cholesterol by a mean of 9 and 16%, respectively (p less than 0.01) in 2 of 13 patients, with no difference in other lipid or lipoprotein parameters in short- or long-term studies.

Adult↗